Multifocal motor neuropathy (MMN) is a slowly progressive disorder of peripheral nerves that is characterized clinically by asymmetric, progressive, predominantly distal weakness in the upper extremities (Pestronk, A. et al., 1988, Ann. Neurol. 24:73-38; Kornberg, A. J. and Pestronk, A., 1995, Ann. Neurol. 37:S43-S50; Parry, G. J., "Motor neuropathy with multifocal conduction block", pp. 1518-1524 in Peripheral Neuropathy (Dyck, P. J. and Thomas, P. K., eds.), 3rd ed., W. B. Saunders, Philadelphia, 1993). Arms are involved more frequently than legs, and there is generally no bulbar, upper motor neuron, or sensory involvement (Bird, 1990, Current Opinion Neurol. Neurosurg. 3:704-707). Electrodiagnostic studies show focal blockage of impulse conduction along motor axons (Pestronk, A. et al., 1988, Ann. Neurol. 24:73-38; Parry, G. J., "Motor neuropathy with multifocal conduction block", pp. 1518-1524 in Peripheral Neuropathy (Dyck, P. J. and Thomas, P. K., eds.), 3rd ed., W. B. Saunders, Philadelphia, 1993). In more than eighty percent of patients, weakness begins in the hands and may progress slowly for periods up to twenty years. MMN is more common in males than females (2:1) and frequently (66 percent) begins in patients younger than 45 years of age.
Previous studies have shown that serum IgM antibodies to GM1 ganglioside are common in MMN, having been reported in 30% to 63% of patients (Kornberg, A. J. and Pestronk, A., 1995, Ann. Neurol. 37:S43-S50; Kornberg, A. J. and Pestronk, A., 1994, Muscle Nerve 17:100-104; Sadiq, S. A. et al., 1990, Neurology 40:1067-1072; Adams, D. et al., 1991, Neuroimmunology 32:223-230; Taylor, B. V. et al., 1996, Neurology 46:951-955). The target of serum antibodies, if any, in the remaining patients has been unclear. It has recently been found that IgM in patient sera binds to GM1 ganglioside as a component in a lipid mixture, GGC (GM1 ganglioside, galactocerebroside, and cholesterol sulfate) more commonly than to GM1 ganglioside alone (Pestronk, A. et al. (1997), Neurology 48:1104-1106). Enzyme-linked immunosorbent assays (ELISA) have been used for identification of antibodies to GM1 ganglioside (see, for example, Pestronk, A. et al. (1990), Ann. Neurol. 27:316-326; U.S. Pat. No. 5,443,952; and U.S. patent application Ser. Nos. 08/137,895, 08/481,144 and 08/789,86; the entire teachings of this reference, patent and patent applications are incorporated herein by reference in their entirety).
Electrophysiological testing in search of motor conduction block during the workup of MMN can be time consuming and, in some cases with severely affected nerves or equivocal findings, difficult to interpret. In addition, some immune-mediated motor neuropathies may not have conduction block. In these motor neuropathies antibody testing may be the only objective method of distinguishing the neuropathy from other motor neuron disorders such as amyotrophic lateral sclerosis (ALS). It is important to clarify the diagnosis, as immune disorders are often treated with modalities that are very expensive or associated with significant side effects. Methods of diagnosing motor neuropathies based on specific disease-related criteria would facilitate identification of treatable disease, reduce the time and expense associated with electrophysiological testing, and expedite commencement of treatment.